Defective genes may be implicated in the development of Alzheimer's disease. Epidemiologic case control studies, family pedigree analysis and recent studies in twins clearly indicated that inherited gene defects are involved in the development of this disease (Schellenberg et al, 1995).
Two different genes whose mutations is associated with early onset familial Alzheimer's disease have been recently identified (Levy-Lahad et al, 1995, Campion et al, 1995, Nechiporuk et al, 1993, Rogaev et al, 1995, Broeckhoven et al, 1992, George-Hyslop et al, 1992, David F et al, 1988, Yoshizawa et al, 1993). They include a gene on chromosome 14 called S182 (presenilin 1) and a candidate gene for the chromosome 1 Alzheimer's disease (AD) locus called STM2 (presenilin 2).
A point mutation in the STM2 resulting in the substitution of an isoleucine for an asparagine (N1411) was identified in affected people from Volga German AD kindreds. Presence of the missense mutation supports the hypothesis that the mutation is pathogenic (Ley-Lahad et al, 1995).
Clinical and neuropathologic features of chromosome 14-linked familial Alzheimer's disease (14qFAD) in affected members of the L family was reported (Lampe et al, 1994). Common features include early onset dementia before the age of 50, early progressive aphasia, early-appearing myoclonus and generalized seizers, paratonia, cortical atrophy, numerous and extensive senile plaques, neurofibriallary tangles, and prominent amyloid angiopathy (Lampe et al, 1994). The clinical and neuropathologic features in four (FAD4, FAD2, A, B) of six additional recently defined 14-q-linked FAD kindreds conformed to that seen in the L family (Lampe et al, 1994). In presenile Alzheimer's disease, recent memory, information-processing speed, sequential tracking, and conceptual reasoning were the earliest congnitive functions that were affected. Later, progressive congitive deficits and inability to perform the daily activities occured. (Farlow et al, 1994). Death occurred about 6 years after the onset of the disease. Autopsy revealed presence of cerebral amyloid deposits and neurofibrillary tangles (Farlow et al, 1994).
The genetic defect in familial Alzheimer's disease does not seem to be tightly associated with the amyloid beta-protein gene which is found in the senile plaques, cerebrovascular amyloid deposits and neurofibrillary tangles (Tanzi et al, 1987).
Clinical characteristics in a kindred with early-onset Alzheimer's disease and their linkage to a G-->T change at position 2149 of the amyloid precursor protein gene.
Neurology 44, 105-11 (1994)
[94119354]
(Similarity score 60) (View Citation format,Abstract format,MEDLARS format,ASN.1 format, or 30 MEDLINE neighbors
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Screening of the mis-sense mutation producing the 717Val-->Ile substitution in the amyloid precursor protein in Japanese familial and sporadic Alzheimer's disease.
J Neurol Sci 117, 12-5 (1993)
[94015131]
(Similarity score 60) (View Citation format,Abstract format,MEDLARS format,ASN.1 format, or 30 MEDLINE neighbors)
Defective genes may be implicated in the development of Alzheimer's disease. Epidemiologic case control studies, family pedigree analysis and recent studies in twins clearly indicated that inherited gene defects are involved in the development of this disease (Schellenberg et al, 1995).
